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Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population.

ABSTRACT: BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. RESULTS Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661-rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). CONCLUSIONS Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population.

SUBMITTER: Xiao S

PROVIDER: S-EPMC4755665 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population.

Xiao Shan S Zeng Xiaoyun X Fan Yong Y Su Yinxia Y Ma Qi Q Zhu Jun J Yao Hua H

Medical science monitor : international medical journal of experimental and clinical research 20160213

BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated wi ...[more]

PMID: 26873362

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Project description:Studies have showed a number of susceptibility genes variants such as transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), juxtaposed with another zinc finger protein 1 (JAZF1) and HNF1 homeobox B (HNF1B) been strongly associated with type 2 diabetes (T2D) in various ethnic groups. However, few studies have conducted in Uyghur, a Chinese minority ethnic group as an admixture population of Caucasians and East Asians. This study was performed to evaluate the association of genetic polymorphism with T2D susceptibility in the Uyghur population. The genomic samples from the blood of unrelated 284 T2D patients and 258 healthy controls were genotyped and analyzed using denaturing high performance liquid chromatography (DHPLC) assay. We found that four SNPs (rs290487, rs864745, rs4430796 and rs23136) in TCF7L2, JAZF1, HNF1B and KCNQ1 genetic regions show unique association with T2D in Uyghur population with an OR of 6.67295% (CI 1.06-1.48, P=0.002), an OR of 0.302 (CI 1.21-1.53, P=0.005) and an OR of 0.223 (CI 0.98-1.17, P=0.001), respectively. Subjects with mutant CC genotype of rs290487 were at high increased risk of T2D in Uyghur especially for the male subjects with an OR=11.782 (CI 1.12-1.53, P=0.001). Further metabolic evaluation confirmed that subject with rs290487 genotype have higher waste-hip circumference ratio (P<0.05), diastolic blood pressure (P<0.05), fasting blood glucose (P<0.05) and hemoglobin A1c levels (P<0.05). While mutant AA genotype for rs23136 (OR=0.223, CI 1.03-1.44, P=0.002) respectively were a protective factor in the Uyghur population. The rs231362 have also found been associated with fasting blood glucose and high-density lipoprotein respectively (P<0.05). However, none of the genotypes showed the significant association with T2D in local Han Chinese population. Taken together, we confirmed the rs290487, rs231362 and rs4430796 transcription variants may act as genetic risk factors for the development of T2D in the Uyghur population in China and these results might provide supporting evidences for T2D diagnosis for Uyghur people in the future.

Dataset Information

Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population.

Publications

Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population.

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